The role of digital health in palliative care for people living with HIV in sub-Saharan Africa: A systematic review

Background In 2018, 26.6 million people were living with HIV in sub-Saharan Africa. Palliative care services are recommended for people living with HIV at all stages from diagnosis through to end-of-life. However, the provision of palliative care in sub-Saharan Africa is limited, leading to little or no access for the majority of patients. Digital technologies in sub-Saharan Africa present an opportunity to improve access to palliative care for people living with HIV in the region. This review synthesised literature on digital health interventions for palliative care for people living with HIV in sub-Saharan Africa and assessed their effects on patient outcomes. Methods Literature searches were conducted in MEDLINE, Embase, PsycINFO and Global Health. Inclusion and exclusion criteria were applied. Two independent reviewers conducted study screening, data extraction and quality appraisal. A narrative synthesis was performed to draw together and report findings across heterogeneous studies. Reporting of this review follows the Preferred Reporting Items for Systematic Review and Meta-Analysis checklist. Results Out of 4117 records, 25 studies were included, covering 3592 people living with HIV, across 21 countries. Studies included three randomised controlled trials, three qualitative, three pre- and post-test, two observational, two case series, six cross-sectional and six mixed methods studies. Telemedicine was the most reported digital health intervention, with 12 studies demonstrating the effectiveness of digital health interventions. Conclusion Emerging evidence suggests digital health interventions can be effective in facilitating patient-provider communication and health professional decision-making as a part of palliative care for people living with HIV. There is a need for further development and evaluation of digital health interventions alongside determining optimal approaches to their implementation as a part of palliative care provision in sub-Saharan Africa.


Introduction
In 2018, 37.9 million people were living with HIV (PLWH) globally and 26.6 million (68%) were from sub-Saharan Africa (SSA). 1 Antiretroviral therapy (ART) has transformed the HIV pandemic into a chronic disease. 2 There is a need for palliative care for PLWH as it is an integral part of HIV care from diagnosis to end of life. 3 PLWH have a high prevalence of psychological and physical symptoms, including worry, anxiety, depression, diarrhoea, constipation and insomnia. 4 When accessed, palliative care can improve patient outcomes across multiple domains. 5 Palliative care involves the prevention and relief of physical, emotional, social or spiritual suffering associated with any chronic or life-threatening illness, is fundamental to health and human dignity and is a basic human right. 6 Palliative care is an essential service within universal health coverage 7 ; in 2014, a World Health Assembly Resolution called on national governments to carry out actions to develop and strengthen palliative care. 8 Despite the need for palliative care and its positive impact on patient outcomes, coverage in SSA is greatly below need, 9 driven by a multitude of factors including unavailability, isolated services, limited funding, lack of inadequate policy and inadequate referral practices. 10 The application of digital health approaches as health systems strengthening tools has been highlighted through WHO guidance. 11 The application of information and communication technologies systems can be used to deliver one or more digital health interventions including, for example, systems for client communication, telemedicine, health management information and electronic medical records. 12 Digital health technologies can be leveraged through existing palliative care models in SSA (see Table 1) to improve access to palliative care by reaching patients in remote areas, 13 providing e-learning to healthcare providers 14 and routinely collecting data to inform policy. 15 SSA is the fastest growing consumer market for mobile phone services with 456 million unique mobile subscribers in 2018 (44% penetration rate) and is estimated to reach 623 million subscribers (50% penetration rate) by 2025. 16 Digital innovation in SSA is being driven by mobile phones. 16 The Essential Palliative Care Package for Universal Health Coverage 17 highlights digital health as an approach to increasing access to palliative care services. A systematic review 18 of literature up until 2015 found that in SSA, mobile phones are starting to be used to improve access to palliative care by enabling patients to communicate with providers, [19][20][21] to encourage patients to adhere to appointments 22 and for health provider education. 23 However, the evidence underpinning digital health for palliative care in SSA is still underdeveloped. 24 Emerging evidence suggests the potential of digital technologies to support PLWH with self-management, medication adherence and facilitating communication with health professionals. 25,26 However, to date, there have been no reviews with a focus on digital health approaches for palliative care among PLWH in SSA. This review addresses the gap by synthesising existing literature to date and reporting on the effectiveness of digital health interventions on patient outcomes.

Objectives
This review addresses two questions: (a) What digital health interventions are being used to provide palliative care to PLWH in SSA? (b) What is the effectiveness of identified digital health interventions on patient outcomes? A population, intervention, comparator, outcomes and study (PICOS) framework was used to structure the review. This included people living with HIV in SSA (population), digital health (intervention/exposure), usual care or no comparator (comparison), physical, psychological, social or spiritual symptoms, a focus on quality of life, patient satisfaction with palliative care services, and other patient outcomes relevant to palliative care (outcomes). This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). 27 A full protocol is registered in PROSPERO (reference number: CRD42020182695).

Eligibility
Included studies included PLWH, a digital health intervention (defined broadly as the use of information and communications technology in support of health and health-related Table 1. Three models of palliative care in SSA. Models of palliative care in SSA as reported in Downing et al. (2015) 69 Description of model Community Healthcare workers deliver palliative care in the homes of patients 76 or at a selected location within the community 77 and make referrals to the district level where appropriate. 69 Caregivers also provide palliative care within the home of the patient. 19 District hospital Palliative care is provided to both outpatients and in-patients referred from the community level for further care or from specialists for continued management. 78,79 Specialist Palliative care is usually provided by specialist teams or doctors at tertiary hospitals who receive referrals from facilities at lower or a similar level. 78,80 SSA: sub-Saharan Africa.
fields 28 ) involving palliative care patients and/or providers, reported patient outcomes and were conducted in SSA. Studies with or without comparators were also included, alongside studies where digital health was part of a combined intervention package. Any study design or setting (e.g. community and hospital) was included. Articles published in any language were eligible for inclusion. Studies were excluded if they had patients with diseases other than HIV, no digital health intervention, did not report patient outcomes and were conducted outside SSA. Studies with digital health interventions used in HIV prevention, testing, ART adherence and viral load monitoring were excluded except when the intervention was explicitly used to support palliative care for PLWH. Studies were also excluded if they did not report primary data.

Search of studies
Search strategies (see Supplementary Material 1) were developed with guidance from information specialists at the university of the lead author. Literature searches were conducted in MEDLINE, Embase, PsycINFO and Global Health on 22 May 2020 with no limit on publication date. The search strategies were adapted with relevant Boolean operators and search characters for each database. A combination of search terms for 'HIV', 'Digital Health' and 'sub-Saharan Africa' was used to capture all digital health literature in HIV care for the SSA region. Combinations of MeSH terms and keywords were used to search the databases. EndNote X9 was used to store and manage the references exported from the databases alongside identifying and removing duplicate citations.

Study selection and data collection
Two reviewers (CM and MJA) independently reviewed titles and abstracts against the inclusion and exclusion criteria. Full-text articles were sought for the included studies and their content was assessed against the inclusion and exclusion criteria. Any disagreements between the two reviewers were resolved through discussion. KN reviewed the final list of the selected studies. Figure 1 presents the PRISMA flow diagram 27 for this review. A data extraction form was developed based on the Cochrane Collaboration 29 and converted into an Excel spreadsheet. The spreadsheet was used to extract and store data from the included studies (see Supplementary Material 2

Risk of bias assessment
The Mixed Methods Appraisal Tool 32 was used to assess the risk of bias for the individual studies (see Supplementary Material 4). CM appraised the studies and MJA reviewed the appraisal. Any discrepancies were resolved through discussion. KN cross-checked the final appraisal.

Statistical analysis
Due to the heterogeneity of the included studies, a descriptive synthesis 33 was used to summarise the included studies. This was followed by a classification of the digital health interventions by the WHO taxonomy 30 and descriptions of the interventions according to the TIDieR checklist. 31 A framework for the development of complex interventions 34 was also used to describe the stages of development of digital health interventions described in included studies.

Results
In total, 4117 records were identified. After de-duplication, 2207 articles remained. The articles were screened and a full-text review carried out for 43 articles. Following fulltext review, 25 articles were included in the review. Included studies used quantitative (n = 22) and qualitative (n = 3) study approaches (see Figure 1).

WHO classification Study TIDieR description
Targeted client communication 46 Mobile phones were used to facilitate communication between healthcare providers and patients (including their treatment supporters). The communication included medication and clinic appointment reminders. This review was interested in the psychosocial support the PLWH received from their healthcare providers and treatment supporters. Software was used to automate sending of the SMSs to patients and treatment supporters. PLWH received the intervention in a community setting. 41 Mobile phones were used to provide acceptance and commitment therapy to pregnant HIV-positive women to improve their psychological flexibility. Software automated the sending of SMSs to patients. The intervention included one face-to-face session within a clinic setting and was followed by weekly SMSs to mobile phones of the patients in their community. 42 Mobile phones were used to provide remote counselling to adolescents living with HIV to improve their self-care capacity and adjustment to their illness. SMS, voice calls, multi-media and WhatsApp messages were used to administer the intervention. Healthcare workers made the voice calls and sent the messages. The adolescents received the intervention in their community. 48 The study explored the acceptability of using mobile phones among PLWH to improve retention in care and adherence to treatment. This review was interested in the 'retention in care' component of the study because of its potential application to palliative care for PLWH. No intervention was administered to the participants.
Client to client communication 40 Social media support groups were used to provide HIV knowledge to adolescents living with HIV and to help the adolescents get social support, adhere to ART and stay in care. Online facilitators provided training, administered quizzes and moderated discussions. Participants were given data and feature phones to access the virtual groups. Initial face-to-face meetings were held by participants and their facilitators to agree on ground rules for the virtual support groups. The virtual support groups were used as a complementary to clinic visits. 57 HIV-positive youth stable in care, provide social support to newly diagnosed HIV-positive youth through mobile phones. Phone calls, SMS and WhatsApp were used as communication channels. The virtual peer mentors guided newly diagnosed HIV-positive youth through the healthcare system. The mentors would conclude the mentorship process by inviting the mentees to a youth-adherence club. 58 A chatroom of a social media platform was used to facilitate continued social support among HIV-positive youth who attended the same youth club. There was a moderator for the chatroom. Participants were given airtime to access the chatroom. The chatroom was complementary to clinic visits. 53 A social media platform was used as a peer-support system to improve HIV/ART knowledge. Online moderators run a question and answer (Q&A) section of the platform. Participants used either their own electronic devices or computers installed in their clinics. The intervention was complementary to clinic visits.
Personal health tracking 43 Computer rehabilitation therapy was used as a palliative care intervention to improve cognitive skills for HIV-positive children. Multi-level brain training exercises were administered as part of a computer game that the children played. The intervention was administered face-to-face to individual children. Neuropsychologists decided which (continued)  44 Computer rehabilitation therapy was used as a palliative care intervention to improve cognitive skills for HIV-positive children. Participants were controls from an earlier study. 43 The intervention was multi-level brain training exercises administered as part of a computer game. The intervention was administered face-to-face to individual children. Trainers for the games were undergraduate psychologists/social workers. African content was used in the game. The intervention was administered in both clinic and community settings. 47 Used digital storytelling as a psychosocial palliative care therapy for HIV-positive youth. The youth were mentored by a media expert and paediatric/adolescent HIV nurse counsellor to change negative narratives that dominated their lives to more positive narratives. The youth used computers to create their own stories and share with others. The study was conducted at an non-governmental organisation office that was familiar and safe for the children.
Citizen based reporting 45 PLWH, sex workers and MSM were provided with in-person, online and SMS interventions to report cases of discrimination when accessing healthcare, housing and other services to a government human rights body. The human rights body helped the complainants seek redress. This review was interested in the aspect of utilising digital technologies to tackle discrimination against PLWH as discrimination affects the psychological health of PLWH. 81 Study participants utilised the online and SMS reporting in a community setting.
On demand information services to clients 51 The study 51 explored some digital health interventions for provision of information to HIV-positive MSM in combination with other non-digital interventions. The study 51 had both development and pilot phases. The development phase considered a mixture of digital and non-digital interventions including patient centred care, peer navigators, discrete pill carriers, pill taking/appointment reminders, information sharing on the internet and a telephone hotline. However, it appears that only patient centred care provided by healthcare workers, peer navigators (ART experienced MSM) and discrete pill carriers were tested in the pilot phase. The peer navigators provided guidance to ART naïve MSM using mobile phones and face-to-face. This review was interested in the potential to provide palliative care information and social support to HIV-positive MSM through the hotline and internet. The interest of the review also extended to use of mobile phones by ART experienced MSM to provide social support to ART naïve MSM to help them navigate HIV care. The study was conducted in both clinic and community settings.
Healthcare provider decision support 59 The intervention was software designed to standardise delivery of HIV counselling by health workers to PLWH. The intervention was administered face-to-face using a tablet. It was used for both individual and group counselling in a clinic setting. 56 An application was used to diagnose neurocognitive impairment in HIV-positive patients. The intervention was delivered by lay health workers who were trained how to administer the app through a tablet. The app was administered to patients face-to-face in a clinic setting. 50 The intervention was software designed to standardise delivery of HIV counselling by health workers to PLWH. It was administered through a computer face-to-face in a clinic setting. The intervention was used for individual counselling.
(continued) The intervention was intended at diagnosing skin conditions in PLWHIV. A nurse who came face-to-face with patients received a few days training on how to use a dermatology application on a phone. The nurse captured and forwarded skin and oral images of patients using a mobile phone to a secure password protected site. Internet was used to support this store and forward technique. Remote dermatology experts reviewed the images. The diagnoses and treatment recommendations of the remote experts were compared to an onsite US board certified dermatologist whose diagnoses and treatment recommendations were used as the gold standard. The intervention was delivered in a clinic/hospital setting. 38 This is another report on the above study. 37 35 Tele-sonography was used to diagnose HIV-associated extrapulmonary tuberculosis (TB).
A local physician with one-week training in abdominal ultrasound had face-to-face consultations with patients. The physician was supported by a remote expert in live online interactions during patient examination. The examinations were done in a clinic, 36 The intervention was used to diagnose and recommend treatment for neurological symptoms of different diseases. This review focused on the use of the intervention in PLHIV. Local healthcare workers who interacted face-to-face with the patients received 3-4 weeks training. The local healthcare workers forwarded patient history, examination and their questions to a remote neurologist using internet through a web platform. The intervention was provided in health centres. 39 Remote cervical cancer screening was provided to HIV-positive women. Medical students took in-person photos of the cervixes of the women with a mobile phone camera. The students underwent a day's training in taking the pictures. The photos were transmitted by multi-media messaging (MMS) and stored in a database for evaluation by nurse midwives. The photos were also shared with a remote expert gynaecologist for evaluation. The use of MMS eliminated the need for internet at the clinic where the intervention was provided. 49 Evaluators carried out face-to-face neurocognitive development testing in HIV-affected children. The evaluators had college education and underwent one-week basic neurodevelopment assessment training. They videotape themselves while assessing each child and uploaded videos online where quality assurance centre staff remotely access the files for review. There was also an onsite supervisor that provided support to the evaluators in addition to the remote experts. The setting in which the intervention was provided is unclear. 54 Tele-sonography was used to diagnose HIV-associated extrapulmonary TB. Local health workers that came face-to-face with the patients had a 4-day training on focused assessment with sonography for HIV (FASH). The healthcare workers captured and sent images to a remote United States board-certified radiologist with expertise in ultrasonography. The intervention was administered in a hospital setting.
Referral coordination 52 The study 52 explored the need for an mHealth intervention to help coordinate linkage to clinics for HIV-positive patients found through a home-based HIV testing program delivered by community health workers (CHWs). No intervention was tested. This review was interested in the potential of the intervention to link PLWH to counselling and other palliative care services among a host of HIV care services provided at HIV clinics.
Laboratory and diagnostic imaging management 55 The intervention diagnosed atrial fibrillation (AF) in HIV-positive patients to prevent complications of untreated atrial fibrillation such as ischemic stroke. The goal was to (continued) evaluation stage. Only one study 45 reported research at the implementation stage (see Figure 2).
Reported efficacy and effectiveness of digital health interventions. Both efficacy and effectiveness of digital health interventions are reported in 13 of the 25 included studies. 37,39,[41][42][43][44]49,50,[53][54][55][56][57] A full RCT 41 assessed the efficacy and a pre-post-test study 42 assessed the effectiveness of targeted client communication: (a) delivery of acceptance and commitment therapy through SMS was efficacious in improving psychological flexibility of pregnant HIV-positive women, 41 and (b) mobile phone counselling was also effective in improving psychological outcomes of undisclosed HIV positive youth. 42 A mixed methods and pre-post-test study evaluated the effectiveness of client-to-client communication 53,57 : (a) providing psychosocial support to HIV-positive youth through mobile phones was effective in getting them to commence ART and complete viral load tests, 57 and (b) peer psychosocial support through a social media platform was effective in improving adherence intentions for HIV positive youth. 53 A pilot RCT 43 assessed the efficacy and a pre-post-test study 44 assessed the effectiveness of personal health tracking interventions. 43,44 Computer rehabilitation therapy was efficacious in improving the neurocognitive skills of HIV-positive children. 43 Computer rehabilitation therapy was also effective in improving neurocognitive skills of HIV-positive children. 44 The effectiveness of healthcare provider decision support interventions was assessed in a cross-sectional study, 56 and the efficacy of healthcare decision support interventions was also assessed in a pilot RCT 50 : (a) a mobile phone application was effective in diagnosing neurocognitive impairment in HIV-positive patients, 56 and (b) HIV counselling through a digital platform was efficacious in improving psychosocial outcomes of HIV positive adults. 50 Two cross-sectional studies 37,39 and two observational studies 49,54 assessed the effectiveness of telemedicine interventions: (a) teledermatology was not effective in diagnosing and recommending treatment for skin conditions of PLWH, 37 (b) remote diagnosis of cervical cancer in HIV-positive women was effective, 39 (c) teleultrasonography was effective in supervising medical personnel that diagnosed HIV associated tuberculosis 54 and (d) a remote quality assurance centre was effective in helping neurodevelopment evaluators maintain the quality of their testing. 49 A prospective cross-sectional study assessed the effectiveness of a laboratory and diagnostics imaging management intervention. 55 A portable electrocardiogram (ECG) device was effective in generating readable ECGs in patients with the World Health Organisation AIDS Clinical Staging (WACS) of 1 only. 55 Table 5 details included studies outlining the efficacy and effectiveness of digital health interventions for provision of palliative care in PLWH in SSA.

Discussion
There is an emerging evidence base of good quality research to inform digital health interventions for the provision of palliative care to PLWH in SSA. In SSA, digital health has been used to provide palliative care to PLWH through targeted client communication, client-to-client communication, personal health tracking, citizen-based reporting, on-demand information services to clients, healthcare provider decision support, telemedicine, referral coordination and laboratory and diagnostics imaging management. Most interventions were at the stages of feasibility, piloting and evaluation. Of the included studies, efficacy was reported across three studies and effectiveness across 10 studies for digital health interventions seeking to improve intended outcomes. Whilst previous research has focused on SMS interventions, 60 there are now multiple, broader digital health approaches being developed and tested to support patients with HIV and palliative care needs. However, further evidence is needed to understand how the effectiveness of interventions is realised and how they can best be integrated into the routine delivery of palliative care services.
Telemedicine was the most researched digital health intervention for palliative care in PLWH. A human resource gap in SSA, particularly at the primary care level, has been highlighted 61 with telemedicine posing a potential approach to addressing the shortage of expertise. However, the use of telemedicine was limited to provider-to-provider communication in a clinical setting making it mostly applicable to the district hospital and specialist palliative care models. In SSA, there is scope to explore telemedicine in the provision of palliative care for PLWH by extending its use to facilitate provider-client communication. In developed countries, telemedicine has been used to remotely manage pain and other symptoms, expanding the reach of palliative care services. 62 It has also been used to coordinate patient care, minimising utilisation of outpatient services 63 while improving the provider-client relationship. 64 Such an approach, encouraging telehealth programs to enable, for example, families to virtually visit and partake in health decisions with loved ones, has been a recommendation of the World Health and Palliative Care Alliance in response to the COVID-19 pandemic. 65 Critical to expansion to approaches is the need to accommodate low digital health literacy for both providers and patients, alongside other known barriers including the cost of delivering telemedicine and telecommunication and infrastructure challenges (e.g. intermittent electrical supply, limited mobile phone network coverage), especially in rural areas. 66 Additional, research is needed in SSA to determine the cost, available infrastructure for digital health, and acceptability of telemedicine among patients and providers. The second most researched digital health interventions for palliative care were targeted client communication and client-to-client communication. The underlying theme across both categories was the use of digital health to provide psychosocial support to PLWH, with a great need for psychosocial support reported previously among PLWH. 67 Studies conducted in several SSA countries found the prevalence of mental illness among PLWH to be 19% or higher. 68 This review found that the use of digital health psychosocial interventions among PLWH occurred in both community and clinical settings, suggesting their potential appropriateness across different models of palliative care in SSA (i.e. community, district and specialist). 69 Digital health interventions that provide counselling and peer support may be an approach to supporting psychosocial symptoms among PLWH in SSA, with a number of the interventions having demonstrated acceptability and effectiveness in assessing, monitoring and treating severe mental illnesses in LMICs. 70 The literature on the use of digital health to support palliative care in SSA is at an early stage and there remains a need to understand the needs and preferences of PLWH and the services delivering palliative care to inform the requirements of digital health interventions. A review 71 of successful approaches for scaling up digital health interventions in LMICs found that interventions that align with need are more likely to be adopted and engaging for end-users. In addition, understanding user needs helps reduce health inequalities by ensuring the engagement of vulnerable groups from the outset. 72 Alongside determining user needs, future research exploring digital health for PLWH in SSA needs to explore the mechanisms that underpin and mediate any changes to outcomes arising from interventions. Exploring such mechanisms in well-established digital health approaches (e.g. telemedicine) may offer intervention agnostic insights that could inform the development of less common approaches that have value for PLWH in SSA. Such findings may also have relevance beyond the SSA region as the lack of an evidence base and end-user involvement in digital health interventions for PLWH is an issue across many LMICs. 73 Within this review, only one study 41 developed a digital health intervention underpinned by an existing theory. Exploring opportunities for applying and developing underlying theories that can inform digital health intervention development is a crucial next step in developing the research  There was no comparator to the intervention. The average total score of the evaluators at baseline was 161 (range: 118-180), after 10 months of the QA centre's supervision the average total score was 178 (range: 175-180), and the average total score for the last video evaluators had submitted to the QA centre was 165 (range: 140-180). The authors considered these rubric scores sufficient because a mean score greater than 70% of the maximum score is what was required.
(continued) 24 DIGITAL HEALTH field. 74 Furthermore, exploring cost-effectiveness evaluation of digital health interventions that have demonstrated effectiveness in improving patient outcomes is necessary to facilitate scale-up and wider adoption, with cost a central consideration for government decision-making around intervention adoption. 75

Strengths and limitations
To our knowledge, this is the first systematic review to explore the role of digital health in palliative care for PLWH in SSA. This review utilised robust search strategies with broad inclusion criteria, including any study design. This review is, however, limited by the fact that no searches were undertaken in grey literature databases and that hand-searching was not done due to time limitations. As a result, while we are confident of the inclusion of a wide body of literature, it may not reflect the entirety of relevant research literature.

Conclusion
Research into the use of digital health interventions to support palliative care for people living with HIV in SSA is developing. However, there is a lack of a theoretical underpinning to many interventions, the mechanisms through which interventions lead to change in patient outcomes are not clear, and most reported interventions have not progressed to a stage of implementation as part of routine care. Future research should focus on embedding theory into intervention development for PLWH, exploring the potential of additional digital health interventions beyond primarily telemedicine approaches, and aligning intervention development with the wider regional need for the expansion of palliative care provision.